Journal article

Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation

Jeannine Diesch, Megan J Bywater, Elaine Sanij, Donald P Cameron, William Schierding, Natalie Brajanovski, Jinbae Son, Jirawas Sornkom, Nadine Hein, Maurits Evers, Richard B Pearson, Grant A McArthur, Austen RD Ganley, Justin M O'Sullivan, Ross D Hannan, Gretchen Poortinga



The three-dimensional organization of the genome contributes to its maintenance and regulation. While chromosomal regions associate with nucleolar ribosomal RNA genes (rDNA), the biological significance of rDNA-genome interactions and whether they are dynamically regulated during disease remain unclear. rDNA chromatin exists in multiple inactive and active states and their transition is regulated by the RNA polymerase I transcription factor UBTF. Here, using a MYC-driven lymphoma model, we demonstrate that during malignant progression the rDNA chromatin converts to the open state, which is required for tumor cell survival. Moreover, this rDNA transition co-occurs with a reorganization of rDN..

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Funding Acknowledgements

We thank Richard Tothill for helpful discussions. We thank Tim Semple and Gisela Mir Arnau and the Peter Mac Molecular Genomics Core Facility for their contributions to this study. We also thank Kerry Ardley and the Peter Mac Animal Core Facility for their assistance with the mice used in this study. We thank Jason Ellul and Maria Doyle from the Peter Mac Research Computing Facility for their assistance with the bioinformatics associated with this work. This work was supported by project and program grants (R.D.H., G.A.M., and R.B.P.) from the National Health and Medical Research Council (NHMRC) of Australia and also Cancer Council of Victoria and Leukaemia Foundation of Australia grants in aid (G.P., G.A.M., and R.D.H.). The researchers were funded by the following: NHMRC fellowships (R.D.H., R.B.P., and G.A.M.) and a Sir Edward Weary Dunlop fellowship (G.A.M.).